PIERRE ANDRIEU/ AFP PHOTOIn the preface of Du vrai, du beau, du bien: une nouvelle approche neuronale (Odile Jacob, 2008, Paris), one of the newest books on the dissemination of science by the respected 75-year old neurobiologist Jean-Pierre Changeux, the philosopher Claude Debru summarizes the major achievements of the scientific itinerary of his fellow countryman as follows, in a free translation: “He discovered allostery and developed the allosteric model of the functioning of proteins with Jacques Monod and Jeffries Wyman; the isolation and the identification of the first neurotransmitter receptor, the acetylcholine receptor, itself an allosteric protein; he then developed a learning model through the selective stabilization of synapses; more recently, he created a model of consciousness in the form of a theory of the neuronal space of conscious work, together with Stanislas Dehaene.”
This is a highly precise summary, covering a fruitful path that began with coli bacilli in order to understand the workings of a bacterial regulating enzyme, L-threonine deaminase. This led to two discoveries about allosteric proteins, as mentioned by Debru, along with one of the most famous scientific articles ever published in the field of molecular biology: “On the nature of allosteric transitions.” Written jointly with his advisor Jacques Monod, one of the 1965 Nobel laureates in Medicine, the paper, which by coincidence was also published in 1965, has since amassed 5,889 citations, an extraordinary figure. Indeed, the 600 articles published by Changeux during the course of his career now account for almost 48,500 citations.
A highly creative scientist, whose eyes focus on the fundamental mechanisms that regulate the biology of any life form, Changeux soon extrapolated the allosteric protein model to neurotransmitter receptors. And it was to test this theoretical proposition that he reached his second considerable experimental achievement, the isolation of the acetylcholine receptor. Thus, on a solid basis of theoretical and experimental molecular biology, the calm French scientist continued to pursue other findings about the most fascinating organ of living beings, the human brain, having arrived, among other items, at the material, biological and biochemical basis of consciousness. This strictly scientific construction was erected on a terrain of fertile, densely humanistic and philosophical culture, which is at the heart of Changeux’s education and on which he keeps his feet firmly planted. Therefore, he is able to extend this to the reader very forcefully in his books on the dissemination of science, including the one he wrote jointly with the philosopher Paul Ricoeur, La nature et la règle. Ce qui nous fait penser (Odile Jacob, 1988, Paris). Changeux always considers science within the arena of culture – but without ever abandoning a “physicalist vision,” as he himself calls it, based on molecular mechanisms.
The following interview was granted by Jean-Pierre Changeux, a mild and polite gentleman, even when he describes extremely vigorous experiments or clarifies complex concepts for lay people, in his office at the Pasteur Institute, on July 8 last. Along with the Collège de France, the Pasteur Institute has been one of his “homes” for his entire lifetime.
Would you rather we start with the biological foundations of consciousness, or with an overview of your work?
Let’s start with the overview, because this will allow me to explain my ideas about consciousness in the context of the work that I have done in the past.
So let’s talk about your first discovery. You discovered allostery and developed the allosteric model of the functioning of proteins along with Jacques Monod and Jeffries Wyman.
Exactly. I began in 1961. This work on allosteric proteins, I believe, is at the origin of a view of life – and therefore of the functions of the brain – that rests on a relatively simple molecular mechanism of transduction of biological signals. The work I did for my thesis, with Jacques Monod, aimed firstly at understanding the workings of a bacterial regulating enzyme, L-threonine deaminase, which was involved in a process of feedback. Threonine deaminase is the first enzyme of the biosynthesis chain in the coli bacillus bacterium and it is inhibited by the final product of the chain. Therefore, the functioning of the chemical chain is regulated. This first enzyme has a catalytic activity – it is a catalyst for an enzyme reaction – while also recognizing and being capable of modifying its activity as the result of a signal that is the final product of the biosynthesis chain. It’s a molecule that has a sort of dual specificity: recognizing and transforming the substrate, receiving and transmitting the regulating signal. Therefore, it is a kind of model of elementary biological regulation.
And how did you get to this enzyme?
Studies on these enzymes already existed; I didn’t discover them; my intention was to understand the regulation mechanism. And based on the studies I produced and that others produced concurrently, I was able to dissociate the enzymatic activity from the regulating activity. In other words, I was able to obtain an enzyme that was still active, but that wasn’t regulated any more by the end product of the biosynthesis chain, a sort of disassembled enzyme. So this enabled me to understand the mechanism of assembly, as it was possible to disassemble the enzyme. One has two sites, two different regions, which are reconnected among themselves by a conformation change. And consequently one gets a sort of processor that conducts critical regulation at a particular node of the metabolism.
So it’s not an electrical connection?
No, it’s a protein whose conformation changes, a sort of molecular mechanism that is evident at the molecular level and even at the level of the organization of the molecule’s atoms. Electrical charge may or may not intervene, but there are connections that only intervene in the structure of the proteins. Therefore, right from the start, we have here a new category of proteins that were given the name of allosteric proteins. They have two regions and, according to the conclusions that we reached, my advisor at the time, who was Jacques Monod, and I, they are in a way models of elementary regulating systems. At the end of my thesis, I generalized this idea for molecules of this type that were presumably in the membrane and that would intervene in the communication between nervous cells; therefore, I pointed out the relation between an elementary bacterial mechanism and an intercellular regulation signal – although in bacteria it is intracellular. Additionally, in this thesis, I put forth the idea that the neurotransmitter receptors at the level of a synapse – which is the contact point between nerve cells – might be allosteric proteins. And then I spent my entire life working on this theme. So the work of my thesis was a work that inaugurated an entire philosophy for understanding living beings and the central nervous system and, therefore, the brain.
All at the same time?
Essentially, yes. The philosophy of molecular biology, first understanding how our brain operates at the molecular level and then identifying the first neurotransmitter receptor.
ALBUM / AKG-IMAGES/ARCHIVES CDA/ST-GENèS/AKG-IMAGES/LATINSTOCKThe receptor of nicotine?
That’s right. As there was no well-known receptor for me to truly test the idea that the neurotransmitter receptors might be allosteric proteins, it was necessary to isolate one. So I turned to the receptor that was the best known one at the time, which had been especially worked on by Sir Henry Dale in England, the neuromuscular junction receptor – which is the acetylcholine receptor because acetylcholine is its neuromediator. Only the pharmacology of this receptor was known, but not its structure, and we didn’t even know whether it was a protein. However, it’s also a nicotine receptor. Indeed, Sir Henry Dale had classified the acetylcholine receptors into various categories: nicotinic and muscarinic; the nicotinic one is connected to an electrical property change whereas the muscarinic one has metabolic effects. So I focused on the nicotinic receptor of the neuromuscular junction, which had been deeply studied by another Englishman, John Newport Langley. As far back as the early twentieth century, Langley had shown that this receptor is blocked by curare and stimulated by nicotine. The problem was to discover how to isolate it, because it is a molecule found only in minute amounts and it is difficult to mark. Today, there are hundreds of identified receptors, but back then, there were none. At first, I resorted to the electrical organ of an electric fish, the electric eel, which, actually, is found in Brazil. Carlos Chagas worked a lot with this fish, which lives in the basin of the Amazon river; however, another such fish is the torpedo, from the Arcachon basin in France.
Yes, it is an elasmobranchi, close to rays. It is flat, lives on the bottom of the sea and produces very powerful electrical discharges. Its electrical organ is extremely rich in cholinergic synapses, all of them identical, therefore very rich in receptors. It was necessary to find a marker to isolate the receptor, and it turned out to be the toxin from a snake venom that made it possible to identify it.
And when did you start to work with this receptor at the brain level?
I began with the electrical organ, which is a huge collection of synapses of the neuromuscular junction type. Then, as soon as the methods of molecular genetics were made available for neurobiologists, this receptor was cloned and sequenced, first in the electrical organ, then in the brain. This gave us access to the brain’s nicotinic receptor.
You explore the different roles of this receptor in the human brain.
Yes. Actually, the human brain is highly sensitive to nicotine, as everybody knows, which is why smokers become users of and dependent on nicotine, which acts upon the brain’s nicotinic receptor. There is also a homologue of the muscular receptor in the brain that acts upon stimulating effects and nicotine dependence. What is very interesting is that we recently managed to show, in the laboratory, that there are very similar receptors in bacteria: in the Gloeobacter, a photosynthetic bacterium, and in other species as well. These bacterial receptors are not sensitive to acetylcholine, but they are sensitive to other regulating signals, such pH. When the pH becomes acid, its ionic channel, whose properties are very similar to those of the nicotinic receptor, opens.
Once again, an overview of life…
Yes. First, it is evidently very important to have a bacterial receptor because in general, it crystallizes more easily and one can establish its structure from the start, using X-ray crystallography. This was done. This made it possible to examine the allosteric transition of these receptors. So, you see, this issue, raised 50 years ago, can now be demonstrated thanks to these bacterial receptors. Another very interesting thing on both the evolutionary and the global level is that bacteria invented, in a way, this type of very uncommon receptor, which is pentamerous and which goes through a membrane with a very particular ionic channel. And what is surprising is that the brain’s receptors are neighbors of the bacterial receptors. This means that we have in our brain, as it were, proteins whose ancestors arose billions of years ago in bacteria. And this receptor has been conserved in our brains! As you see, not everything was invented in man’s brain when he first appeared on Earth. We inherited many structures that were developed earlier.
Based on this parallelism of the cells in our brain and bacterial structures, you have developed a fairly unique view. Could you talk about this a little?
One can’t understand living beings and their brains in particular, other than after understanding the elementary mechanisms that are at the basis of the fundamental functions. In the case of bacteria, we’re talking about the entire metabolism; in other words, we’re talking about the chemical reactions that are elementary for survival and for the reproduction of bacterium cells. At the brain level, the important thing is to understand the relations between the nerve cells, and these relations are unique, because, as you know, the brain is the only organ that forms a network in which the cells establish multiple contacts among themselves. There are about 10 thousand connections per nerve cell, so we’re talking about an extremely complex network. And this is what makes the brain original and what allows it to acquire functions that are as elaborate as reason, consciousness, social life. Thus, the idea that results from these early works on bacteria and on their extension to the communication between nerve cells is that, at the end of the day, our brain functions might be understandable based on the elementary molecular mechanisms for carrying and, above all, for transmitting signals at the level of the synapses. Hence, the physicalist view, in a way. This means that understanding molecular mechanisms is necessary; in other words, all our brain functions go through these molecular mechanisms. When one applies local anesthesia to extract a tooth, or general anesthesia for surgery, one sees that there is a direct connection between the anesthetic, which is a chemical molecule, and consciousness and the perception of pain. This means that there is a chemistry of consciousness and it also means that all these higher functions are rooted in these molecular mechanisms. However, this is not enough: to go further, it is indispensable to understand the organization of the system, to understand how it organizes itself to reach the so-called higher brain functions or cognitive functions, which intervene in the acquisition of knowledge. This is my overall philosophical idea.
Let’s go back to the view of the brain as a network. I don’t know what things are like in France, but in Brazil and in the United States, there is a debate about a global view of the brain vs. a site-oriented view.
I think that the two theories are different but do not exclude each other. I think that there are some places in the brain that are extremely precise, in the tradition of Gall’s phrenology, for instance, the visual areas, the hearing areas, the areas specializing in seeing colors or recognizing faces, while there is also – and here we address the thesis on consciousness – a system of long-distance connections that are susceptible to establishing links, relations, among multiple areas of the brain. Therefore, there is globalism and unity, at the same time, diversity and specialization.
MARTINE FRANCK / MAGNUM PHOTOS / LATINSTOCKAfter the acetylcholine receptor discoveries, you developed a learning model through the selective stabilization of synapses.
This is very important in order to understand how the complexity in our brain works. Let us first examine the genetic level, the evolution of the sequence of the genomes of the mouse, of the monkey and then man, passing through chimpanzees, and we will realize that the differences are very small. Of course, they do exist, because a monkey is not a man and a mouse is not a monkey. So, evidently, there are some very important genetic bases. However, when one examines the number of genes, of structures, one sees that the genome is very close, almost identical, in all mammals. Actually, the number of genes of the drosophila isn’t very far from the number of genes of man. This may seem surprising. And it obviously gives rise to a paradox: does the complexity of the brain rise dramatically whereas that of the genome changes relatively little during the course of evolution? Evolution advances – we already talked about this in connection with the receptors – through the progressive accumulation of elementary structures that were formed in bacteria, then in the eukaryotes, in the multi-cell organisms, in the invertebrates, vertebrates, mammals, etc. And these structures accumulate after each other, so that little by little a brain was built with the complexity of the human brain. Many structures were selected before man appeared, but what actually characterizes the evolution of man? First, the increase in the size of the brain. This is not very hard to understand, all you have to do is to increase the number of cell divisions and just a few genes can take care of this. Then there are certain general organization principles, such as the relative development of the prefrontal cortex, which is very important in man; still, a few development genes determine this organization. However, this is not enough to solve the paradox. A new idea is to take into account the fact that the brain in man is built progressively over 15 years. Its weight increases five-fold as from birth. During this time, the brain develops in constant interaction with the external environment. There is in some way a genetic package that enables these networks to become organized and, afterwards, interaction with the external world specifies them and validates them. This is the idea of selective stabilization of synapses, of synaptic epigenesis that I developed with Antoine Danchin. There is a succession of stages of synaptic exuberance and of selection due to interaction with the physical, social and cultural environment; certain synapses were eliminated and others, conserved, stabilized and amplified. In a way, there is Darwinism at play, not genetic, but epigenetic. This is why I qualified this theory as “epigenesis through the selective stabilization of synapses.”
Are experiments about this theory possible?
Yes, of course. We were able to demonstrate this with the neuromuscular junction and showed that in the stage of synaptic exuberance, if the system is electrically stimulated, the elimination of synapses speeds up. The experiment was also conducted by Lubert Stryer and Carla Shatz at the visual system level. Overall, electrical stimulation entails synaptic elimination. One can also show that when there’s electrical stimulation, there is synaptic elimination. The same occurs at the cerebellum level. Therefore, it’s a very general mechanism, studied by many American researchers.
Is it possible to establish a relation between this theory and the results of functional magnetic resonance?
Yes, but the epigenesis theory is a synaptic and therefore microscopic theory, whereas magnetic resonance exams are macroscopic. So it’s difficult. However, one can observe, for example, that the surface of certain cortical territories is limited during the course of development or remodels itself as the brain of the child develops. One can have tests of this theory that are in a way macroscopic, for instance, by following the progressive structuring of the territories enervated by the eye, the ear or other sensory entry points. I say this as an example; it’s feasible. Still, the real demonstration of the theory occurs at the elementary level, at the synaptic level.
But does the brain make this selection all the time?
Yes, during the course of development, the growth stages of exuberant development and of synaptic selection follow each other, creating a critical stage of interaction with the environment each time. And this is valid even for an adult, I suppose. These multiple stages overlap. And, among others, those that intervene in the learning of spoken language and of written language.
Claude Debru said, in the preface to one of your books, that you recently created a model of consciousness in the form of a theory of the neuronal space of conscious work, developed jointly with Stanislas Dehaene. Can you tell us about this?
Yes, precisely. The critical starting point is experimentally managing to measure access to consciousness; in other words, using objective scientific methods – the images methods, among others – to track the access of signs from the external world to the person’s consciousness, such as a visual sign, a picture or a written text. How can one monitor access to consciousness? By comparing the conscious and non-conscious treatment of the same signal. Biophysical methods that have been known for a long time, called masking, make it possible to do this. You show a person successive slides on a time scale that is of the order of several tens of milliseconds [ms]. The first condition: one shows, for 70 ms, for instance, a written word that is slotted between empty slides before and after the word, and the person is able to say: “Ah, I saw the word lion,” or “I saw the word brain.” Therefore, there is a type of access to consciousness, as the individual is able to say: “Yes, I read the word lion.” But if you now present the same word placing immediately “masks” before and after the word, i.e., figures that are different from the written word, and you ask the person: “Can you see anything?” the person will say “no.” So the same word can be read, or seen consciously, and, on the other hand, enter the brain and propagate within it without consciousness. In the latter case, you find, after the experiment, that the non-conscious processing actually did take place because the person became able to make choices influenced by the word that was treated by the brain in a non-conscious manner. One can, therefore, determine an experimental protocol for submitting humans to a visual test under conditions of consciousness and non-consciousness and, in these two conditions, submit the person to an NMR or EEG. One can correlate objective data about the activity of the brain and the subjective data of the conscious and non-conscious processing. Thus, you can determine, in a way, the neural bases of conscious treatment in relation to non-conscious treatment.
It’s like providing a biological basis for Freud, for example.
Yes, but I don’t like referring to Freud because the major difference is that, in the present case, it’s a scientific study on access to consciousness, and not a literary discourse. What I mean to say by this is that one can, under certain experimental conditions, record measurable parameters through images, through electroencephalography or magneto-encephalography, and obtain physical signals from the brain that correspond to conscious and non-conscious processing.
In your recent revision article, you say the word conscience is rich in ambiguity.
Yes, it’s true. Because there’s moral conscience, political conscience, etc. And also conscience in the physiological sense of the term, which is what is of interest here, and what makes us conscious when we read, when we look at a landscape. When we sleep, we are no longer conscious.
Is access to consciousness what you’re interested in?
Yes. Evidently, the brain must be in a state of consciousness and must not be asleep, anesthetized or in a coma – conditions under which neither the brain nor the individual are conscious. And one can show that there are physiological differences during a coma, during general anesthesia or during sleep. An individual in a coma has no access to consciousness, in theory. Or he or she may have, but very little. In the so-called vegetative states, the individual wakes up and falls asleep, but access to consciousness is strongly altered. The person perceives only a very few things.
And in the case of schizophrenia?
Our interpretation is that a schizophrenic suffers an alteration of the conscious neuronal workspace, which means access that is more restricted. The person will have disturbances in his or her social relations with others because the relationship with another person goes through access to consciousness.
And what are the future challenges for these studies on access to consciousness?
The first thing is consciousness itself. It’s under way. Several research groups are studying what is called self-consciousness, which can be lost selectively, for example, in the case of anogsonosia. An individual with a lesion in the right hemisphere, at the parietal level, will develop hemiplegia on the left side. However, with certain types of lesion, the individual will deny that he or she is paralyzed and lacks any perception of this paralysis of his or her own body. Therefore, there is an alternation of the consciousness of the self and of the body. And this is something that must be understood, of course. Another thing that I’m very interested in is gaining access to what one might call conscious thinking, the organization of thought.
Is tPersonal archivehat possible?
I believe that we’ll manage to do this, undoubtedly.
Is it experimentally possible?
Well, first one must get theoretical results. In this case, I think that the theory is indispensable before or concurrently with experimentation. One indispensible stage is having a neuronal representation of the conscious object, a conscious representation regarding a non-conscious representation. And once you get this, then trying to understand how these conscious representations are susceptible of being linked together, to be joined in order to make up a sentence such as “the sky is blue.” It’s something that should be done and we’re still a long way away from getting to this, but I’m fairly optimistic. I believe that in the next 5 to 10 years this kind of problem may be solved. So I think we will get to a scientific and objective understanding of the organization of thought.
Is this possible?
I believe we’ll achieve this, most certainly.
An objective view of the organization of thinking also corresponds to a view of the organization of language.
Yes, access to language is essential. Language can play a very important role in that it helps to form these conscious representations with the use of words and the sense ascribed to a given word. There might be thought process with representations without words, but certainly words play a very important role. So, it’s the entryway to language and also to social interaction, since language intervenes in social communication. As you can see, there’s still a lot to be done.
Currently, what does your research focus on?
There are three major themes that interest me: on one hand, the transduction of signals by allosteric proteins; understanding how a receptor works at the atomic level, for instance, with the bacterial receptor. The second thing that interests me a lot is the expression of the genes that go hand in hand with epigenesis, to try to correlate the genome with the organization of the brain, first during the course of development and, evidently, in the adult stage. It’s an issue of gene expression during the course of development in relation to the selection of the synapses. And then, the third, is what we just said, trying to make progress in the understanding of the neural bases of conscious representations. It’s currently work that is under way with Stanislas Dehaene and a student of ours. The idea is to address issues that touch upon mathematics, linguistics and the like, with conscious representations as the starting point. This is a little further into the future, but it’s a future that is… concrete.
In parallel with your scientific studies, you have worked on the dissemination of science.
Yes, I have taught at the Collège de France and I write books based on these lectures. I don’t like TV and other media much; written books are more suitable for scientific work, because science requires particularly precise and rigorous explanations. However it’s obvious that there are also other methods, such as TV, or theatre; why not?
You have an overview of culture, of art, and you establish a relationship between science and culture. It is possible to continue along this path?
It’s not only possible but also necessary, from my viewpoint. I think that science develops, the amount of knowledge produced during the last century is considerable, and the danger is for physicists to do only physics or biologists only biology, psychologists only psychology, etc. I think that there must be, to the contrary, a unification of knowledge, beyond the diversity of the disciplines. Actually, that was Diderot’s proposal. What is done in neurosciences should be useful for psychology, what is done in physics should be useful for molecular biology, and the other way around; the issues raised by molecular biology should interest physicists, or the problems raised by experimental psychology should cause physicists to develop new tools to examine with high resolution the states of brain activity in time and in space, simultaneously. So, for me, it’s not only indispensible to have an encyclopedic view, but also to manage to produce multidisciplinary, constructive syntheses. And this includes the humanities because, for us, the brain is directly in contact, it is what produces culture. And culture acts upon the brain. It’s a two-way street. We produce language, but a baby learns language from the language of adults.
How many hours a day do you work?
Hmmm, I don’t count them. As far as I’m concerned, this isn’t a problem, because working, in a way, is restful for me. Not working is what anguishes me; so I don’t count the hours I work, it’s all the time. Evidently, I have many distractions, because, at the same time, in my scientific activity, there are several levels of concentration. There is work that is much more specific, much more in depth, such as the three themes I mentioned a few moments ago; in addition, I am interested in and reflect about art, painting, music, ethical issues, all of which generate debate and air ideas, as it were. I work all the time! And this doesn’t bother me. However of course, you must have family life at the same time.
Were you born in France?
Yes, in the region of Paris. However, my parents weren’t from Paris. My mother came from Rouergue, in the south of France. My grandfather was an elementary school teacher in the village, one of the so-called “black hussars of the Republic;” in other words, people who dedicated their life to lay, free, mandatory education.
So there was an education tradition in the family.
Ah, yes, this is very important; it came from my mother’s side. And my father was an engineering technician who came from central France. These are poor regions. My parents left their regions because they were too poor, they couldn’t find work there. So they came to Paris to work and they met.
How many students have you trained over the course of all these years?
I don’t know. Dozens, undoubtedly. I haven’t worked it out. Perhaps 80 or more. In my laboratory, I had 5 to 7 university students, on average, and the same number of post-doctors, which added up to 10 to 15 people, constantly, for 30 years. It”s a lot of people. And many are professors at highly renowned universities. Stanislas Dehaene, who was one of my part-time students, is a professor at the Collège de France; others are research directors at CNRS, the National Center for Scientific Research; another one teaches at Harvard, another, at Caltech; one was a professor at the University of Tokyo and now works in Riken, Japan. So, most of them are successful. It makes me happy.
Does your group of neuroscientists work in collaboration with groups from other countries?
Yes. Many are foreign; there are many Americans, many Japanese, among those who do post-doctorates. I haven’t received very many South-Americans, unfortunately, because I would’ve liked that. Europeans, Germans, English. It’s always fairly multinational. It’s quite important to keep up the international side in scientific research.
Do you believe that neuroscience is destined to achieve new fundamental developments?
Yet, it’s the future. It’s the science of the future, of what is to come. Physics still has things to discover. A lot is known about the atom, about the structure of matter, about the galaxies. However, there’s still a lot to be done. I believe that the chief unknown factor now is man’s brain… Understanding what we are. What man is.
Have you been interested in science since your childhood?
Yes. As I said, I come from a very modest family that had no interest in science; they didn’t know what this was, and they didn’t even have much of an interest in culture. However, at school, some of the teachers gave me guidance. By the age of 11, a teacher of natural sciences, Jean Bathellier, had strongly encouraged the interest I had in natural science at the time. I collected insects, plants, etc. He helped me and, above all, put me into contact with a famous entomologist from the Museum of Natural History, Eugène Séguy. So by the age of 12 or 13, I was already aware of what research was. At the age of 19, I joined the laboratory of Banyuls-sur-Mer, where I prepared a little thesis: it was there that I discovered a new species of parasitical crustaceans, holothurians, which are echinoderms called sea cucumbers. So I’ve always been passionate about scientific work. It’s my life. I never looked for this! I have always pursued my passion, it’s spontaneous in me.
Do you believe we are in a new world?
Yes I do.
And how do you see this world?
As in all worlds, the important thing is knowing what men will make of it. Look at physics: atomic energy makes it possible to produce electricity and survive, but one can also make bombs with it and kill people. Man did both. So, concerning work on the brain, one must take care that it is used for the good of humankind and not for its destruction.